The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis

Yosuke Akiba, Akiko Mizuta, Yoshito Kakihara, Juri Nakata, Jun Nihara, Isao Saito, Hiroshi Egusa, Makio Saeki

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK-RANKL (receptor activator of nuclear factor κB ligand) signaling has been shown as a main signal pathway for osteoclast differentiation. However, the molecular mechanism and the factors regulating osteoclastogenesis remain to be fully understood. In this study, we performed a chemical genetic screen, and identified a Cdks/GSK-3β (cyclin-dependent kinases/glycogen synthase kinase 3β) inhibitor, kenpaullone, and two Cdks inhibitors, olomoucine and roscovitine, all of which significantly enhance osteoclastogenesis of RAW264.7 cells by upregulating NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) levels. We also determined that the all three compounds increase the number of osteoclast differentiated from murine bone marrow cells. Furthermore, the three inhibitors, especially kenpaullone, promoted maturation of cathepsin K, suggesting that the resorption activity of the resultant osteoclasts is also activated. Our findings indicate that inhibition of GSK-3β and/or Cdks enhance osteoclastogenesis by modulating the RANK-RANKL signaling pathway.

Original languageEnglish
Pages (from-to)253-258
Number of pages6
JournalBiochemistry and Biophysics Reports
Volume5
DOIs
Publication statusPublished - 2016 Mar 1

Keywords

  • Cdks inhibitor
  • GSK-3β inhibitor
  • Osteoclast

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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